title: Acute cardiorespiratory effects of intracisternal injections of mercuric chloride.
abstract: The present studies were conducted to changes arising from mercury poisoning in the central nervous system (CNS), with a focus on determining the receptors and neurotransmitters involved. Currently, little is known regarding the neurological basis of the cardiopulmonary effects of mercury poisoning. We evaluated changes in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), respiratory rate (RR) and heart rate (HR) following a 5 μl intracisternal (i.c) injection of mercuric chloride (HgCl(2)) and the participation of the autonomic nervous system in these responses. 58 animals were utilized and distributed randomly into 10 groups and administered a 5 μL intracisternal injection of 0.68 μg/kg HgCl(2) (n=7), 1.2 μg/kg HgCl(2) (n=7), 2.4 μg/kg HgCl(2) (n=7), 60 μg/kg HgCl(2) (n=7), 120 μg/kg HgCl(2) (n=3), saline (control) (n=7), 60 μg/kg HgCl(2) plus prazosin (n=6), saline plus prazosin (n=6), 60 μg/kg HgCl(2) plus metilatropina (n=4) or saline plus metilatropina (n=4)HgCl(2). Anesthesia was induced with halothane and maintained as needed with urethane (1.2 g/kg) administered intravenously (i.v.) through a cannula placed in the left femoral vein. The left femoral artery was also cannulated to record systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). A tracheotomy was performed to record respiratory rate. Animals were placed in a stereotaxic frame, and the cisterna magna was exposed. After a stabilization period, solutions (saline or HgCl(2)) were injected i.c., and cardiopulmonary responses were recorded for 50 min. Involvement of the autonomic nervous system was assessed through the i.v. injection of hexamethonium (20 mg/kg), prazosin (1 mg/kg) and methylatropine (1 mg/kg) 10 min before the i.c. injection of HgCl(2) or saline. Treatment with 0.68, 1.2, 2.4 μg/kg HgCl(2) or saline did not modify basal cardiorespiratory parameters, whereas the 120 μg/kg dose induced acute toxicity, provoking respiratory arrest and death. The administration of 60 μg/kg HgCl(2), however, induced significant increases (p<0.05) in SAP at the 30°, 40° and 50° min, timepoints and DAP at the 5°, 10°, 20°, 30°, 40° and 50° timepoints. RR was significantly decreased at the 5°, 10°, 20°, 40° and 50° min timepoints; however, there was no change in HR. Hexamethonium administration, which causes non-specific inhibition of the autonomic nervous system, abolished the observed cardiorespiratory effects. Similarly, prazosin, a α(1)-adrenoceptor blocker that specifically inhibits sympathetic nervous system function, abolished HgCl(2) induced increases in SAP and DAP without affecting HR and RR. Methylatropine (1 mg/Kg), a parasympathetic nervous system inhibitor, exacerbated the effects of HgCl(2) and caused slow-onset respiratory depression, culminating in respiratory arrest and death. Our results demonstrate that increases in SAP and DAP induced by the i.c. injection of mercuric chloride are mediated by activation of the sympathetic nervous system.
authors.affiliation: Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Espirito Santo, Espírito Santo, Brazil. brunafernandes.azevedo@gmail.com
authors.forename: Bruna Fernandes
authors.initials: BF
authors.lastname: Azevedo
authors.forename: Henrique de Azevedo
authors.initials: Hde A
authors.lastname: Futuro Neto
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
authors.forename: Dalton Valentin
authors.initials: DV
authors.lastname: Vassallo
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002946:Cisterna Magna / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D020262:Mercury Poisoning, Nervous System / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D008845:Microinjections; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D010276:Parasympatholytics / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000187:drug effects*; D013997:Time Factors
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D004785:Environmental Pollutants; D018733:Nicotinic Antagonists; D010276:Parasympatholytics; D008627:Mercuric Chloride